A Study to Learn About COVID-19 Bivalent BNT162b2 Omicron Containing Vaccine in Healthy Children

Sponsor

BioNTech SE (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05543616

Collaborator

Pfizer (Industry)

2,270

Enrollment

Arms

28.7

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this clinical trial is to learn about the safety, extent of the side effects, and immune responses of the study vaccine (called bivalent BNT162b2 Omicron containing vaccine) in healthy children. The trial is divided into 4 individual studies or substudies based on age group and prior history of COVID-19 vaccinations. All participants in each of the 4 sub-studies study vaccine as a shot depending on what group they are in.

Substudy A design: includes participants 6 months through 23 months who have not received a previous coronavirus vaccination (COVID-19 vaccine naïve) and will receive 3 doses of study vaccine as their initial which may be followed by a fourth dose of study vaccine.
Substudy B design: includes 6 months through 4 years who have either received 2 or 3 prior doses of bivalent BNT162b2 and will receive study vaccine as their third or fourth dose.
Substudy C design: includes participants 6 months through 4 years who have received 3 prior doses of bivalent BNT162b2 and will receive study vaccine as their fourth dose.
Substudy D design: includes participants 5 through 12 years who have received 2 or 3 prior doses of bivalent BNT162b2 and will receive study vaccine as their third or fourth dose.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2 Virus Severe Acute Respiratory Syndrome Coronavirus 2 COVID-19	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) Substudy A Ph 2/3 Selected Dose Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) Substudy C Ph 2/3 Selected Dose	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2270 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

A MASTER PHASE 1/2/3 PROTOCOL TO INVESTIGATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BIVALENT BNT162b2 RNA -BASED VACCINE CANDIDATE(S) IN HEALTHY CHILDREN

Anticipated Study Start Date :

Sep 28, 2022

Anticipated Primary Completion Date :

Feb 18, 2025

Anticipated Study Completion Date :

Feb 18, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 3 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1) Injection in the muscle at 0-, 3-, and 11-weeks and 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose Injection in the muscle
Experimental: 6 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1) Injection in the muscle at 0-, 3-, and 11-weeks and 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose Injection in the muscle
Experimental: 10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1) Injection in the muscle at 0-, 3-, and 11-weeks and 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose Injection in the muscle
Experimental: Selected dose, 6 Months to <2 Years (Substudy A, Phase 2/3) - 0/3/11 week primary series Injection in the muscle at 0-, 3-, and 11-weeks and 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) Substudy A Ph 2/3 Selected Dose Injection in the muscle
Experimental: Selected dose, 6 Months to <2 Years (Substudy A, Phase 2/3) - 0/8/16 week primary series Injection in the muscle at 0-, 8-, and 16-weeks and 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) Substudy A Ph 2/3 Selected Dose Injection in the muscle
Experimental: 3 microgram dose, 6 Months to <4 Years 6 Months (Substudy B, Group 1) Injection in the muscle, 2 doses 2 months apart	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose Injection in the muscle
Experimental: 3 microgram dose, 6 Months to <5 Years (Substudy B, Group 2) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose Injection in the muscle
Experimental: 3 microgram dose, 6 Months to <5 Years (Substudy B, Group 3) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose Injection in the muscle
Experimental: 6 microgram dose, 6 Months to <5 Years (Substudy C, Phase 1) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose Injection in the muscle
Experimental: 10 microgram dose, 6 Months to <5 Years (Substudy C, Phase 1) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose Injection in the muscle
Experimental: Selected dose, 6 Months to <5 Years (Substudy C, Phase 2/3) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) Substudy C Ph 2/3 Selected Dose Injection in the muscle
Experimental: 10 microgram dose, 5 to <12 Years (Substudy D, Group 1) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose Injection in the muscle
Experimental: 10 microgram dose, 5 to <12 Years (Substudy D, Group 2) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose Injection in the muscle
Experimental: 10 microgram dose, 5 to <12 Years (Substudy D, Group 3) Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose Injection in the muscle

Outcome Measures

Primary Outcome Measures

Substudy A (SSA) - Ph 1 dose finding, percentage of participants reporting local reactions [for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4]
tenderness at the injection site, redness, and swelling as self-reported on electronic diaries
SSA - Ph 1 dose finding, percentage of participants reporting systemic events [for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4]
fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries
SSA - Ph 1 dose finding, percentage of participants reporting adverse events [from Dose 1 to 1 month after Dose 3 and from Dose 4 to 1 month after Dose 4]
as elicited by investigational site staff
SSA - Ph 1 dose finding, percentage of participants reporting serious adverse events [from Dose 1 to 6 months after the last dose]
as elicited by investigational site staff
SSA - Ph 2/3 selected dose, percentage of participants reporting local reactions [for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4]
tenderness at the injection site, redness, and swelling as self-reported on electronic diaries
SSA - Ph 2/3 selected dose, percentage of participants reporting systemic events [for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4]
fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries
SSA - Ph 2/3 selected dose, percentage of participants reporting adverse events [from Dose 1 to 1 month after Dose 3 and from Dose 4 to 1 month after Dose 4]
as elicited by investigational site staff
SSA - Ph 2/3 selected dose, percentage of participants reporting serious adverse events [from Dose 1 to 6 months after the last dose]
as elicited by investigational site staff
SSA - Ph 2/3 selected dose, superiority with respect to ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥6 months to <2 years of age [at 1 month after 3 doses of bivalent BNT162b2 at the selected dose (on a 0-, 3-, and 11-week schedule) to 1 month after 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
SSA - Ph 2/3 selected dose, noninferiority with respect to seroresponse rate to the Omicron BA.4/BA.5 strain in participants ≥6 months to <2 years of age [at 1 month after 3 doses of bivalent BNT162b2 at the selected dose (on a 0-, 3-, and 11-week schedule) and at 1 month after 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
SSA - Ph 2/3 selected dosed, superiority with respect to ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥6 months to <2 years of age [at 1 month after Dose 3 in participants following a 0-, 8-, and 16-week schedule and those following a 0-, 3-, and 11-week schedule]
As measured at the central laboratory
SSA - Ph 2/3 selected dose, noninferiority with respect to the the seroresponse rate to the Omicron BA.4/BA.5 strain in participants ≥6 months to <2 years of age [at 1 month after Dose 3 in participants following a 0-, 8-, and 16-week schedule and those following a 0-, 3-, and 11-week schedule]
As measured at the central laboratory
Substudy B (SSB) - percentage of participants reporting local reactions [for up to 7 days following Dose 1 (for Groups 1, 2 and 3) and Dose 2 (for Group 1)]
Participants ≥6 months to <2 years of age: tenderness at the injection site, redness, and swelling as self-reported on electronic diaries Participants ≥2 to <5 years of age: pain at the injection site, redness, and swelling as self-reported on electronic diaries
SSB - percentage of participants reporting systemic events [for up to 7 days following Dose 1 (for Groups 1, 2 and 3) and Dose 2 (for Group 1)]
Participants ≥6 months to <2 years of age: fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries Participants ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries
SSB - percentage of participants reporting adverse events [from the first study vaccination to 1 month after the first study vaccination (for Groups 1, 2, and 3), and from the second study vaccination to 1 month after the second study vaccination (for Group 1 only)]
as elicited by investigational site staff
SSB - percentage of participants reporting serious adverse events [from Dose 1 to 6 months after the last dose]
as elicited by investigational site staff
SSB - ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥6 months to <5 years of age [at 1 month after Dose 3 for participants who received 2 prior doses of BNT162b2 3 µg and a third dose of bivalent BNT162b2 to C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
SSB - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain in participants ≥6 months to <5 years of age [at 1 month after Dose 3 between participants who received 2 prior doses of BNT162b2 3 µg and a third dose of bivalent BNT162b2 and C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
SSB - ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥6 months to <5 years of age [at 1 month after Dose 4 for participants who received 2 prior doses of BNT162b2 3 µg and a third and fourth dose of bivalent BNT162b2 to those at 1 month after Dose 3 for C4591007 participants who received 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
SSB - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain in participants ≥6 months to <5 years of age [at 1 month after Dose 4 for participants who received 2 prior doses of BNT162b2 3 µg and a third and fourth dose of bivalent BNT162b2 and at 1 month after Dose 3 for C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
SSB - ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥6 months to <5 years of age [at 1 month after Dose 4 for participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 to those as 1 month after Dose 3 for C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
SSB - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain in participants ≥6 months to <5 years of age [at 1 month after Dose 4 for participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 and at 1 month after Dose 3 for C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg]
As measured at the central laboratory
Substudy C (SSC) - Ph 1 dose finding, percentage of participants reporting local reactions [for up to 7 days following Dose 1]
Participants ≥6 months to <2 years of age: tenderness at the injection site, redness, and swelling as self-reported on electronic diaries Participants ≥2 to <5 years of age: pain at the injection site, redness, and swelling as self-reported on electronic diaries
SSC - Ph 1 dose finding, percentage of participants reporting systemic events [for up to 7 days following Dose 1]
Participants ≥6 months to <2 years of age: fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries Participants ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries
SSC - Ph 1 dose finding, percentage of participants reporting adverse events [1 month after Dose 1]
as elicited by investigational site staff
SSC - Ph 1 dose finding, percentage of participants reporting serious adverse events [6 months after Dose 1]
as elicited by investigational site staff
SSC - Ph 1 dose finding - geometric mean titers elicited by prophylactic bivalent BNT162b2 at each dose level given as a fourth dose in participants ≥6 months to <5 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSC - Ph 1 dose finding - geometric mean fold rise elicited by prophylactic bivalent BNT162b2 at each dose level given as a fourth dose in participants ≥6 months to <5 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSC - Ph 1 dose finding - percentage of participants with seroresponse elicited by prophylactic bivalent BNT162b2 at each dose level given as a fourth dose in participants ≥6 months to <5 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSC - Ph 2/3 selected dose, percentage of participants reporting local reactions [for up to 7 days following Dose 1]
Participants ≥6 months to <2 years of age: tenderness at the injection site, redness, and swelling as self-reported on electronic diaries Participants ≥2 to <5 years of age: pain at the injection site, redness, and swelling as self-reported on electronic diaries
SSC - Ph 2/3 selected dose, percentage of participants reporting systemic events [for up to 7 days following Dose 1]
Participants ≥6 months to <2 years of age: fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries Participants ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries
SSC - Ph 2/3 selected dose - percentage of participants reporting adverse events [1 month after Dose 1]
as elicited by investigational site staff
SSC - Ph 2/3 selected dose - percentage of participants reporting serious adverse events [6 months after Dose 1]
as elicited by investigational site staff
SSC - Ph 2/3 selected dose - the ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥6 months to <5 years of age [at 1 month after Dose 4 for participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 at the selected dose level to those who received a fourth dose of bivalent BNT162b2 3 µg in Substudy B]
As measured at the central laboratory
SSC - Ph 2/3 selected dose - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain for participants ≥6 months to <5 years of age [at 1 month after Dose 4 between participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 at the selected dose level and those who received a fourth dose of bivalent BNT162b2 3 µg in Substudy B]
As measured at the central laboratory
Substudy D (SSD) - percentage of participants reporting local reactions [for up to 7 days following Dose 1]
pain at the injection site, redness, and swelling as self-reported on electronic diaries
SSD - percentage of participants reporting systemic events [for up to 7 days following Dose 1]
fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries
SSD - percentage of participants reporting adverse events [1 month after Dose 1]
as elicited by investigational site staff
SSD - percentage of participants reporting serious adverse events [6 months after Dose 1]
as elicited by investigational site staff
SSD - ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥5 to <12 years of age [at 1 month after bivalent BNT162b2 as a third dose for participants who received 2 prior doses of BNT162b2 10 µg and at 1 month after a third dose of BNT162b2 10 µg for C4591007 Phase 1 participants who received 3 doses of BNT162b2 10 µg]
As measured at the central laboratory
SSD - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain participants ≥5 to <12 years of age [at 1 month after bivalent BNT162b2 as a third dose for participants who received 2 prior doses of BNT162b2 10 µg and at 1 month after a third dose of BNT162b2 10 µg for C4591007 Phase 1 participants who received 3 doses of BNT162b2 10 µg]
As measured at the central laboratory
SSD - the ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥5 to <12 years of age [at 1 month after bivalent BNT162b2 as a fourth dose for participants who received 3 prior doses of BNT162b2 10 µg to at 1 month after a third dose of BNT162b2 10 µg for C4591007 Phase 1 participants who received 3 doses of BNT162b2 10 µg]
As measured at the central laboratory
SSD - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain in participants ≥5 to <12 years of age [at 1 month after bivalent BNT162b2 as a fourth dose for participants who received 3 prior doses of BNT162b2 10 µg and at 1 month after a third dose of BNT162b2 10 µg for C4591007 Phase 1 participants who received 3 doses of BNT162b2 10 µg]
As measured at the central laboratory

Secondary Outcome Measures

SSA - Ph 1 dose finding, geometric mean titers elicited by prophylactic bivalent BNT162b2 at each dose level in COVID-19 vaccine-naïve participants ≥6 months to <2 years of age [At baseline (before Dose 1), 1 month after Dose 2, 1 month after Dose 3 and 1 month after Dose 4]
As measured at the central laboratory
SSA - Ph 1 dose finding, geometric mean fold rise elicited by prophylactic bivalent BNT162b2 at each dose level in COVID-19 vaccine-naïve participants ≥6 months to <2 years of age [At baseline (before Dose 1), 1 month after Dose 2, 1 month after Dose 3 and 1 month after Dose 4]
As measured at the central laboratory
SSA - Ph 1 dose finding, percentage of participants with seroresponse elicited by prophylactic bivalent BNT162b2 at each dose level in COVID-19 vaccine-naïve participants ≥6 months to <2 years of age [At baseline (before Dose 1), 1 month after Dose 2, 1 month after Dose 3 and 1 month after Dose 4]
As measured at the central laboratory
SSA - Ph 2/3 dose finding, geometric mean titers elicited by bivalent BNT162b2 in participants ≥6 months to <2 years of age [At baseline (before Dose 1), 1 month after Dose 3 and 1 month after Dose 4]
As measured at the central laboratory
SSA - Ph 2/3 dose finding, geometric mean fold rise elicited by bivalent BNT162b2 in participants ≥6 months to <2 years of age [At baseline (before Dose 1), 1 month after Dose 3 and 1 month after Dose 4]
As measured at the central laboratory
SSA - Ph 2/3 dose finding, percentages of participants with seroresponse elicited by bivalent BNT162b2 in participants ≥6 months to <2 years of age [At baseline (before Dose 1), 1 month after Dose 3 and 1 month after Dose 4]
As measured at the central laboratory
SSB - geometric mean titers elicited by bivalent BNT162b2 given as third and/or fourth dose in participants ≥6 months <5 years of age [Group 1: At baseline (before Dose 1), 1 month after Dose 1 and 1 month after Dose 2; Groups 2 and 3: At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSB - geometric mean fold rise elicited by bivalent BNT162b2 given as third and/or fourth dose in participants ≥6 months <5 years of age [Group 1: At baseline (before Dose 1), 1 month after Dose 1 and 1 month after Dose 2; Groups 2 and 3: At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSB - percentages of participants with seroresponse elicited by bivalent BNT162b2 given as third and/or fourth dose in participants ≥6 months <5 years of age [Group 1: At baseline (before Dose 1), 1 month after Dose 1 and 1 month after Dose 2; Groups 2 and 3: At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSC - Ph 2/3 selected dose - geometric mean titers elicited by bivalent BNT162b2 at the selected dose level given as a fourth dose in participants ≥6 months to <5 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSC - Ph 2/3 selected dose - geometric mean fold ratio elicited by bivalent BNT162b2 at the selected dose level given as a fourth dose in participants ≥6 months to <5 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSC - Ph 2/3 selected dose - percentages of participants with seroresponse elicited by bivalent BNT162b2 at the selected dose level given as a fourth dose in participants ≥6 months to <5 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSD - geometric mean titers elicited by bivalent BNT162b2 given as a third or fourth dose in participants ≥5 to <12 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSD - geometric mean fold rise elicited by bivalent BNT162b2 given as a third or fourth dose in participants ≥5 to <12 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory
SSD - percentages of participants with seroresponse elicited by bivalent BNT162b2 given as a third or fourth dose in participants ≥5 to <12 years of age [At baseline (before Dose 1) and 1 month after Dose 1]
As measured at the central laboratory

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 11 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Substudy A

Inclusion Criteria:

Healthy male or female participants ≥6 months to <2 years of age, at the time of randomization.

Exclusion Criteria:

Previous or current diagnosis of multisystem inflammatory syndrome in children (MIS-C).
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
Previous vaccination with any coronavirus vaccine.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Substudy B

Inclusion Criteria:

Healthy male or female participants = ≥6 months to <5 years of age, at the time of enrollment.

Exclusion Criteria:

Previous or current diagnosis of MIS-C.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus.
Prior receipt of any COVID 19 vaccine other than BNT162b2.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Substudy C

Inclusion Criteria:

Health male or female participants ≥6 months to <5 years of age, at the time of randomization/enrollment.

Exclusion Criteria:

Previous or current diagnosis of MIS-C.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus.
Prior receipt of any COVID 19 vaccine other than BNT162b2.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Substudy D

Inclusion Criteria:

Healthy male or female participants ≥5 years to <12 years of age, at the time of enrollment.

Exclusion Criteria:

Previous or current diagnosis of MIS-C.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus.
Female who is pregnant or breastfeeding.
Prior receipt of any COVID 19 vaccine other than BNT162b2.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.